In context – long-acting cabotegravir for HIV prevention

Australian researchers reviewed data from the unblinded phase of trial HPTN 083 and noted that infections were distributed as follows:

• long-acting cabotegravir (LA cab) – 12 new HIV infections
• TDF + FTC – 32 new HIV infections

Adherence

According to the Australian researchers, “the majority of new HIV infections in both the long-acting and oral daily PrEP groups occurred in the context of [drug] interruptions or challenges with adherence. This highlights the importance of adherence to PrEP, which notably decreased in both groups during the unblinded phase.”

LA cab is a new technology for HIV prevention. Clinics will need to determine which patients will benefit most from this way of preventing HIV. They will need to find ways to ensure that patients return to clinics for regular injections and screening for HIV and other sexually transmitted infections (STIs).

LA cab—the first long-acting formulation of PrEP—will likely be in demand because of its infrequent dosing schedule, but not everyone who initiates it may be able to stay on it. Also, some people may not want to initiate it because they dislike injections. Therefore, studies will need to be done to find out why some people stop taking long-acting forms of PrEP and whether other forms of HIV prevention can meet their needs.

HIV screening

Regular screening for STIs (including HIV) is a routine part of care for people who take PrEP. The Australian researchers noted that HIV drugs used for PrEP can sometimes result in a delayed diagnosis of HIV in the very rare cases when infections occur. This delay can happen because of the anti-HIV effects of PrEP – these effects initially keep HIV levels low until the virus can develop the ability to overcome PrEP. The researchers underscored that a combination of HIV screening assays, including antibody tests and viral load assays (which seek the genetic material of HIV), should be used in people who are taking long-acting PrEP.

Risk factors

In the HPTN 083 trial, more people taking LA cab experienced a higher rate of issues associated with cardiovascular disease (compared to those taking TDF + FTC). These issues included high blood pressure, abnormal lipid levels (cholesterol) in their blood and “a trend towards increased blood glucose levels.” Although the proportion of such cases was very small, the researchers called for longer-term monitoring in people who take LA cab to better understand which people develop these issues. Also, researchers stated that healthcare providers need to “consider existing comorbidities” when selecting PrEP, particularly for older people.

People use PrEP during seasons of risk and are unlikely to use long-acting or other forms of PrEP permanently. The adverse effects seen in a small proportion of people who used LA cab will likely resolve upon cessation of this drug.

The number of infants born to people who took cabotegravir while pregnant is low in published studies. Further study of cabotegravir during pregnancy is needed.

In clinics

In the everyday world of clinics that prescribe PrEP, studies will need to be done to assess how they are able to deliver LA cab (if they encounter any barriers and how they are overcome) and the proportion of eligible patients who accept and continue to use it over time.

In Canada

Long-acting cabotegravir for HIV prevention has been approved in the U.S., European Union and other regions, where it is sold under the brand name Apretude.

LA cab for prevention will hopefully be approved in Canada by late Spring 2024. Note that after approval by Health Canada, it may take up to three months before private insurance companies agree to place it on their lists of subsidized medicines. The manufacturer of cabotegravir, ViiV Healthcare, will engage in negotiations with provincial and territorial ministries of health over the cost of the drug. If both the company and ministries of health can agree on a price, then LA cab will be subsidized. Typically, such negotiations can take a year, sometimes even longer.

—Sean R. Hosein

REFERENCE:

Griffin DW, Hoy JF, McMahon JH. Long-acting cabotegravir PrEP: a time for cautious optimism. Lancet HIV. 2023 Dec;10(12):e756-e757